Abstract
The development of specific and age-appropriate pediatric formulations is essential to assure that all children and their care-givers can easily access to safe and effective dosage forms. The need for developing specific pediatric medicinal products has been highlighted by the European Medicines Agency. The aim of this study was to investigate the effectiveness of combining the advantages of both cyclodextrin (CD) complexation and loading into nanostructured lipid carriers (NLC), to obtain a liquid oral pediatric formulation of hydrochlorothiazide (HCT), endowed with safety, dosage accuracy, good stability and therapeutic efficacy. Equimolar drug combinations as physical mixture (P.M.) or coground product (GR) with hydroxypropyl-β-cyclodextrin (HPβCD) or sulfobutylether-β-cyclodextrin (SBEβCD) were loaded into NLC, then characterized for particle size, homogeneity, Zeta potential, entrapment efficiency, gastric and storage stability. The presence of HPβCD allowed higher entrapment efficacy than NLC loaded with the plain drug, and enabled, in the case of GR systems a complete and sustained drug release, attributable to the wetting and solubilising properties of HPβCD toward HCT. In vivo studies on rats proved the superior therapeutic effectiveness of HCT-in HPβCD-in NLC formulations compared to the corresponding free HCT-loaded NLC, thus confirming the successfulness of the proposed approach in the development of an efficacious liquid oral formulation of the drug.
Highlights
The development of specific and appropriate pediatric formulations is essential to assure that all children, of different ages, as well as their care-givers, can access to safe and accurate dosage forms
The aim of this study was to investigate the effectiveness of combining the advantages of both cyclodextrin (CD) complexation and loading into nanostructured lipid carriers (NLC), to obtain a liquid oral pediatric formulation of hydrochlorothiazide (HCT), endowed with safety, dosage accuracy, good stability and therapeutic efficacy
No important differences were observed when adding the drug as P.M. or as GR product with HPβCD. All these results indicated that the presence of HPβCD itself did not affect the physicochemical properties and stability of NLC dispersions
Summary
The development of specific and appropriate pediatric formulations is essential to assure that all children, of different ages, as well as their care-givers, can access to safe and accurate dosage forms. The lack of an adequate availability of medicines appositely developed for pediatric use resulted in the last decades in several off-label and unlicensed prescriptions, increasing the risks of adverse drug reactions, which may be more severe or different from those in adults [2]. This problem had as a consequence a wide use of extemporaneous preparations, obtained, starting from formulations for adult people, by dilution of liquid dosage forms or by tablet crushing or capsule opening, leading to administration of drugs with poor/uncontrolled dosing accuracy, unknown stability, variable bioavailability, poor compliance for children and care-givers [3].
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